DESCRIPTION: There has been great interest in whether vitamin D supplementation might hold potential for influencing health in aging HIV-infected populations. An estimated 60% of HIV-infected persons have subclinical vitamin D deficiency. Given the established immunomodulatory role of vitamin D as well as its myriad other functions, there is a firm foundation for hypothesizing vitamin D deficiency might have disease risk consequences for older HIV-infected persons. The underlying motivation for this proposal is to use a more comprehensive approach to understanding the complex relationships between vitamin D metabolite levels and inflammation and how they relate to aging outcomes among HIV-infected persons. The proposed study will measure two vitamin D metabolites (25[OH]D and the active form, 1,25[OH]2D), before and after the critical time point of HAART initiation. With these measures, we will capitalize on an existing platform of inflammatory biomarker data in 500 HIV- infected men to study the complex connections between inflammation, vitamin D metabolism and age-related disease. The study includes participants from four study sites across the United States and collaborators from University of Washington and Johns Hopkins University. The specific aims of this study are: 1) Characterize serum 25[OH] and 1,25[OH]2D levels across strata of age and HIV-status and evaluate the association of each metabolite with available inflammatory markers before and after HAART initiation 2) Determine the association between serum 25[OH] and 1,25[OH]2D levels pre- and post- HAART and both immune reconstitution and chronic disease/geriatric outcomes by age and HIV-status. Understanding how vitamin D metabolism may vary in HIV-infected individuals and impact risk of disease and poor functioning in an aging population is an important issue that will be supported by the proposed epidemiologic research. The biomarkers being evaluated are modifable in terms of their levels in the body and thus have the potential to form the basis of an intervention for lowering risk of disease.